The invention relates to a method of protecting a biologically active substance against denaturation, wherein a liquid containing the active substance and a matrix-forming substance are deposited on a target surface and dried so as to form a solid amorphous matrix with the active substance embedded therein.
Numerous active pharmaceutical ingredient molecules and protein molecules for therapeutic or prophylactic treatment or diagnosis are known to be susceptible to denatuation, e.g. to breakdown or irreversible deformation.
In order to be able to keep the active substances stable during storage at ambient temperature, it has been known to suspend the active molecules in a stabilizing substance which is then transformed into an amorphous solid (glassy) state either by freeze drying or spray drying.
However, freeze drying has the drawback that it requires expensive equipment and long processing times. Further, the active molecules may be damaged by the formation of ice crystals in the freezing process. Frequently, a cumbersome post processing of the freeze-dried product is necessary in order to bring it into a state ready for administration.
On the other hand, spray drying has the disadvantage that a considerable portion of the product remains in the spray dryer, so that the yield of the dried active substance is low. Further, the active molecules may be damaged as a result of exposure to high temperatures during the drying process. Frequently, an additional drying step is necessary in order to reduce the residual moisture.
U.S. Pat. No. 7,354,597 discloses a method wherein microquantities (between 1 nl and 10 pl) of a liquid with the stabilizing substance and the active substance suspended therein are deposited in microscale reservoirs, i.e. concave-shaped structures on a target surface, and are then dried with or without a freezing step. Injection and ink jet printing are mentioned as examples of suitable deposition methods.